Low apolipoprotein A-II levels causally contribute to increased mortality in septic shock
Bibliographic record
Abstract
BACKGROUND: Lipoproteins and their component apolipoproteins play an important role in sepsis. However, little is known with regard to the association and causal contribution of these proteins to mortality in patients of different ancestries following septic shock. The objective of this study was to determine whether lipoprotein and apolipoprotein levels, and related genetic variants, are associated with clinical outcomes in septic shock. METHODS: We investigated the association between lipoprotein and apolipoprotein levels at the point of admission to the intensive care unit and in-hospital mortality in 687 Japan patients diagnosed with septic shock. For each clinically significant candidate protein, we extracted haplotype tag single nucleotide polymorphisms (SNPs) of the corresponding gene and examined the association of the candidate gene variants with 28-day mortality and organ dysfunction. We tested for replication in a Caucasian septic shock cohort (Vasopressin and Septic Shock Trial, VASST, n = 474). To determine whether the candidate lipoprotein causally contributed to septic shock outcome, we used a Mendelian randomization analysis based on polygenic scores generated from a genome-wide association study (GWAS) in the Japan cohort. RESULTS: In the Japan cohort, low apolipoprotein A-II levels were associated with increased septic shock mortality (adjusted odds ratio, 1.05; 95%CI, 1.02-1.09; P < 0.001). For a haplotype tag SNP of the corresponding ApoA2 gene, rs6413453 GG carriers had significantly higher 28-day mortality (adjusted hazard ratio [aHR], 1.79; 95% confidence interval [CI], 1.06-3.04; P = 0.029) and significantly fewer days free of cardiovascular, respiratory, renal and neurologic dysfunction than AG/AA carriers. This result was replicated in the Caucasian septic shock cohort (28-day mortality: aHR, 1.65; 95% CI, 1.02-2.68; P = 0.041). Mendelian randomization using 9 SNPs from an apolipoprotein A-II GWAS suggested that genetically decreased levels of apolipoprotein A-II were a causal factor for increased mortality in septic shock (odds ratio for mortality due to a 1 mg/dL decrease in apolipoprotein A-II is 1.05 [95% CI; 1.01-1.03, P = 0.0022]). CONCLUSIONS: In septic shock, apolipoprotein A-II levels and ApoA2 genetic variations are important factors associated with outcome.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".